Anthracyclinones. Part 3. Use of di-isopropylidene-D-glucose and a modified marschalk reaction to introduce a tertiary carbinol function into ring D of anthracyclinones

Abstract

Reaction of 3-C-ethynyl-1,2-O-isopropylidene-α-D-ribo-pentodiaido-1,4-furanose (2b) with leuco-quinizarin (4) in alkaline solution gave a mixture of (5S)- and (5R)-3-C-ethynyl-1,2-O-isopropylidene-5-(quinizarin-2-yl)-α-D-ribofuranose (11a) and (11b) respectively and the corresponding 5-deoxyderivative (11c). Acid-catalysed hydrolysis of the furanoses (11a) and (11b) furnished the quinizarinyl pyranoses (13a) and (14) respectively. Similarly, 3-O-benzyl-3-C-ethynyl-1,2-O-isopropylidene-α-D-ribo-pentodialdo-1,4-furanose (2c) with leuco-quinizarin gave a good yield of a mixture of the two diastereoisomers(5S)- and (5R)-3-O-benzyl-3-C-ethynyl-1,2-O-isopropylidene-5-(quinizarin-2-yl)-α-D-ribofuranose (11d) and (11e) respectively and reaction of each with boron trichloride resulted in the loss of the benzyl and isopropylidene groups to give the quinizarinylpyranoses (13a) and (14) respectively. Hydrolysis of compound (11d) with acid produced the crystalline (5S)-3-O-benzyl-3-C-ethynyl-5-(quinizarin-2-yl)-α-(β)-D-ribopyranose (13b) which, with periodate, afforded (4S)-2-O-benzyl-2-C-ethynyl-3-O-formyl-4-(quinizarin-2-yl)-α-(β)-D-erythro-tetrofuranose (15). Reduction of compound (15) with zinc and methanolic acetic acid and treatment of the resulting leuco-derivative with 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) in DMF produced the (10S)-8-benzyloxy-8-ethynylhexahydroxyanthracyclinone (17a) and the corresponding deoxy derivative (18a), debenzylation of each of which with boron trichloride gave the corresponding anthracyclinones (17b) and (18b) respectively. Structures of the compounds were confirmed by u.v., mass, i.r., c.d., and ¹H n.m.r. spectroscopy.